What is myoclonus?

Myoclonus describes a symptom and not a diagnosis of a disease. It refers to sudden, involuntary jerking of a muscle or group
of muscles. Myoclonic twitches or jerks usually are caused by sudden muscle contractions, called positive myoclonus, or by
muscle relaxation, called negative myoclonus. Myoclonic jerks may occur alone or in sequence, in a pattern or without pattern.
They may occur infrequently or many times each minute. Myoclonus sometimes occurs in response to an external event or when
a person attempts to make a movement. The twitching cannot be controlled by the person experiencing it.

In its simplest form, myoclonus consists of a muscle twitch followed by relaxation. A hiccup is an example of this type of
myoclonus. Other familiar examples of myoclonus are the jerks or "sleep starts" that some people experience while drifting
off to sleep. These simple forms of myoclonus occur in normal, healthy persons and cause no difficulties. When more widespread,
myoclonus may involve persistent, shock-like contractions in a group of muscles. In some cases, myoclonus begins in one region
of the body and spreads to muscles in other areas. More severe cases of myoclonus can distort movement and severely limit
a person's ability to eat, talk, or walk. These types of myoclonus may indicate an underlying disorder in the brain or nerves.

What are the causes of myoclonus?

Myoclonus may develop in response to infection, head or spinal cord injury, stroke, brain tumors, kidney or liver failure,
lipid storage disease, chemical or drug poisoning, or other disorders. Prolonged oxygen deprivation to the brain, called hypoxia,
may result in posthypoxic myoclonus. Myoclonus can occur by itself, but most often it is one of several symptoms associated
with a wide variety of nervous system disorders. For example, myoclonic jerking may develop in patients with multiple sclerosis,
Parkinson's disease, Alzheimer's disease, or Creutzfeldt-Jakob disease. Myoclonic jerks commonly occur in persons with epilepsy,
a disorder in which the electrical activity in the brain becomes disordered leading to seizures.

What are the types of myoclonus?

Classifying the many different forms of myoclonus is difficult because the causes, effects, and responses to therapy vary
widely. Listed below are the types most commonly described.

Action myoclonus is characterized by muscular jerking triggered or intensified by voluntary movement or even the intention to move. It may
be made worse by attempts at precise, coordinated movements. Action myoclonus is the most disabling form of myoclonus and
can affect the arms, legs, face, and even the voice. This type of myoclonus often is caused by brain damage that results from
a lack of oxygen and blood flow to the brain when breathing or heartbeat is temporarily stopped.

Cortical reflex myoclonus is thought to be a type of epilepsy that originates in the cerebral cortex - the outer layer, or "gray matter," of the brain,
responsible for much of the information processing that takes place in the brain. In this type of myoclonus, jerks usually
involve only a few muscles in one part of the body, but jerks involving many muscles also may occur. Cortical reflex myoclonus
can be intensified when individuals attempt to move in a certain way (action myoclonus) or perceive a particular sensation.

Essential myoclonus occurs in the absence of epilepsy or other apparent abnormalities in the brain or nerves. It can occur randomly in people
with no family history, but it also can appear among members of the same family, indicating that it sometimes may be an inherited
disorder. Essential myoclonus tends to be stable without increasing in severity over time. In some families, there is an association
of essential myoclonus, essential tremor, and even a form of dystonia, called myoclonus dystonia. Another form of essential
myoclonus may be a type of epilepsy with no known cause.

Palatal myoclonus is a regular, rhythmic contraction of one or both sides of the rear of the roof of the mouth, called the soft palate. These
contractions may be accompanied by myoclonus in other muscles, including those in the face, tongue, throat, and diaphragm.
The contractions are very rapid, occurring as often as 150 times a minute, and may persist during sleep. The condition usually
appears in adults and can last indefinitely. Some people with palatal myoclonus regard it as a minor problem, although some
occasionally complain of a "clicking" sound in the ear, a noise made as the muscles in the soft palate contract. The disorder
can cause discomfort and severe pain in some individuals.

Progressive myoclonus epilepsy (PME) is a group of diseases characterized by myoclonus, epileptic seizures, and other serious symptoms such as trouble walking
or speaking. These rare disorders often get worse over time and sometimes are fatal. Studies have identified many forms of
PME. Lafora body disease is inherited as an autosomal recessive disorder, meaning that the disease occurs only when a child inherits two copies of
a defective gene, one from each parent. Lafora body disease is characterized by myoclonus, epileptic seizures, and dementia
(progressive loss of memory and other intellectual functions). A second group of PME diseases belonging to the class of cerebral storage diseases usually involves myoclonus, visual problems, dementia, and dystonia (sustained muscle contractions that cause twisting movements
or abnormal postures). Another group of PME disorders in the class of system degenerations often is accompanied by action myoclonus, seizures, and problems with balance and walking. Many of these PME diseases begin
in childhood or adolescence.

Reticular reflex myoclonus is thought to be a type of generalized epilepsy that originates in the brain stem, the part of the brain that connects to
the spinal cord and controls vital functions such as breathing and heartbeat. Myoclonic jerks usually affect the whole body,
with muscles on both sides of the body affected simultaneously. In some people, myoclonic jerks occur in only a part of the
body, such as the legs, with all the muscles in that part being involved in each jerk. Reticular reflex myoclonus can be triggered
by either a voluntary movement or an external stimulus.

Stimulus-sensitive myoclonus is triggered by a variety of external events, including noise, movement, and light. Surprise may increase the sensitivity
of the individual.

Sleep myoclonus occurs during the initial phases of sleep, especially at the moment of dropping off to sleep. Some forms appear to be stimulus-sensitive.
Some persons with sleep myoclonus are rarely troubled by, or need treatment for, the condition. However, myoclonus may be
a symptom in more complex and disturbing sleep disorders, such as restless legs syndrome, and may require treatment by a doctor.

What do scientists know about myoclonus?

Although rare cases of myoclonus are caused by an injury to the peripheral nerves (defined as the nerves outside the brain
and spinal cord, or the central nervous system), most myoclonus is caused by a disturbance of the central nervous system.
Studies suggest that several locations in the brain are involved in myoclonus. One such location, for example, is in the brain
stem close to structures that are responsible for the startle response, an automatic reaction to an unexpected stimulus involving
rapid muscle contraction.

The specific mechanisms underlying myoclonus are not yet fully understood. Scientists believe that some types of stimulus-sensitive
myoclonus may involve overexcitability of the parts of the brain that control movement. These parts are interconnected in
a series of feedback loops called motor pathways. These pathways facilitate and modulate communication between the brain and
muscles. Key elements of this communication are chemicals known as neurotransmitters, which carry messages from one nerve
cell, or neuron, to another. Neurotransmitters are released by neurons and attach themselves to receptors on parts of neighboring
cells. Some neurotransmitters may make the receiving cell more sensitive, while others tend to make the receiving cell less
sensitive. Laboratory studies suggest that an imbalance between these chemicals may underlie myoclonus.

Some researchers speculate that abnormalities or deficiencies in the receptors for certain neurotransmitters may contribute
to some forms of myoclonus. Receptors that appear to be related to myoclonus include those for two important inhibitory neurotransmitters:
serotonin and gamma-aminobutyric acid (GABA). Other receptors with links to myoclonus include those for opiates and glycine,
the latter an inhibitory neurotransmitter that is important for the control of motor and sensory functions in the spinal cord.
More research is needed to determine how these receptor abnormalities cause or contribute to myoclonus.

How is myoclonus treated?

Treatment of myoclonus focuses on medications that may help reduce symptoms. The drug of first choice to treat myoclonus,
especially certain types of action myoclonus, is clonazepam, a type of tranquilizer. Dosages of clonazepam usually are increased
gradually until the individual improves or side effects become harmful. Drowsiness and loss of coordination are common side
effects. The beneficial effects of clonazepam may diminish over time if the individual develops a tolerance for the drug.

Many of the drugs used for myoclonus, such as barbiturates, levetiracetam,phenytoin, and primidone, are also used to treat
epilepsy. Barbiturates slow down the central nervous system and cause tranquilizing or antiseizure effects. Phenytoin, levetiracetam, and
primidone are effective antiepileptic drugs, although phenytoin can cause liver failure or have other harmful long-term effects
in individuals with PME. Sodium valproate is an alternative therapy for myoclonus and can be used either alone or in combination
with clonazepam. Although clonazepam and/or sodium valproate are effective in the majority of people with myoclonus, some
people have adverse reactions to these drugs.

Some studies have shown that doses of 5-hydroxytryptophan (5-HTP), a building block of serotonin, leads to improvement in
people with some types of action myoclonus and PME. However, other studies indicate that 5-HTP therapy is not effective in
all people with myoclonus, and, in fact, may worsen the condition in some individuals. These differences in the effect of
5-HTP on individuals with myoclonus have not yet been explained, but they may offer important clues to underlying abnormalities
in serotonin receptors.

The complex origins of myoclonus may require the use of multiple drugs for effective treatment. Although some drugs have a
limited effect when used individually, they may have a greater effect when used with drugs that act on different pathways
or mechanisms in the brain. By combining several of these drugs, scientists hope to achieve greater control of myoclonic symptoms.
Some drugs currently being studied in different combinations include clonazepam, sodium valproate, levetiracetam, and primidone.
Hormonal therapy also may improve responses to antimyoclonic drugs in some people.

What research is being done?

Within the Federal government, the National Institute of Neurological Disorders and Stroke (NINDS), a component of the National
Institutes of Health (NIH), has primary responsibility for research on the brain and nervous system. As part of its mission,
the NINDS supports research on myoclonus at its laboratories in Bethesda, Maryland, and through grants to universities and
major medical institutions across the country.

Scientists are seeking to understand the underlying biochemical basis of involuntary movements and to find the most effective
treatment for myoclonus and other movement disorders.

Investigators are evaluating the role of neurotransmitters and receptors in myoclonus. If abnormalities in neurotransmitters
or receptors are found to play a causative role in myoclonus, future research can focus on determining the extent to which
genetic alterations are responsible for these abnormalities and on identifying the nature of those alterations. Scientists
also may be able to develop drug treatments that target specific changes in the receptors to reverse abnormalities, such as
the loss of inhibition, and to enhance mechanisms that compensate for these abnormalities. Identifying receptor abnormalities
also may help researchers develop diagnostic tests for myoclonus. NINDS-supported scientists at research institutions throughout
the country are studying various aspects of PME, including the basic mechanisms and genes involved in this group of diseases.

For more information on neurological disorders or research programs funded by the National Institute of Neurological Disorders
and Stroke, contact the Institute's Brain Resources and Information Network (BRAIN) at:

Prepared by:
Office of Communications and Public Liaison
National Institute of Neurological Disorders and Stroke
National Institutes of Health
Bethesda, MD 20892

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on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined
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